Atrial Natriuretic Peptide　― Old But New Therapeutic in Cardiovascular Diseases ―

Abstract

With the discovery of atrial natriuretic peptide (ANP), the heart as an endocrine organ was established. Basic science revealed that ANP, through the particulate guanylyl cyclase A receptor and cGMP, plays a fundamental role in cardiorenal biology. This work has led to the development of ANP as a therapeutic, especially in heart failure (HF). Human genomics has strengthened our understanding of ANP, revealing specific ANP gene variants that may be associated with biological dysfunction, but also may mediate protective properties, including in metabolic syndrome. Advances in understanding the processing and degradation of ANP molecular forms have resulted in therapeutic breakthroughs, especially inhibition of ANP degradation by neprilysin inhibitors. Although ANP is administered intravenously for acute HF, a novel therapeutic strategy is its chronic delivery by subcutaneous injection. An innovative therapeutic development is engineering to develop ANP-based peptides for chronic use. These interconnected topics of ANP biology and therapeutics will be reviewed in detail.

Stress and Inflammation in Coronary Artery Disease: A Review Psychoneuroendocrineimmunology-Based

“…The administration of ANP, BNP, or CNP may also limit post-infarction ventricular remodeling. In decompensated heart failure, ANP and BNP infusion reduces both pulmonary capillary wedge pressure and systemic vascular resistance, thus enhancing stroke volume [for review: ( 51 , 52 )].…”

Natriuretic peptides in the control of lipid metabolism and insulin sensitivity

“…Strategies aimed to chronically inhibit NP degradation might be a way to sustain appropriate systemic NP levels and thus NP signalling in metabolic tissues. Inhibiting NPRC‐mediated, NEP‐mediated or insulin‐degrading‐enzyme‐mediated NP breakdown could be suitable options in this respect, as recently reviewed . Secondly, NP delivery may be envisioned, a therapeutic option in which adequate delivery is crucial to obtain clinical efficacy .…”

“…Inhibiting NPRC‐mediated, NEP‐mediated or insulin‐degrading‐enzyme‐mediated NP breakdown could be suitable options in this respect, as recently reviewed . Secondly, NP delivery may be envisioned, a therapeutic option in which adequate delivery is crucial to obtain clinical efficacy . In addition to the use of recombinant ANP (carperitide) and BNP (nesiritide) in acute heart failure treatment , the therapeutic potential of these compounds in metabolic diseases may be tested.…”

Supramolecular complex sacubitril/valsartan - the first representative of a new class of drugs for the treatment of chronic heart failure

“…GCR-A and GCR-B mediate all the main effects of NUP in target cells. These are, first of all, the weakening of fibrotic and hypertrophic myocardial damage [13], vasodilation, inhibition of proliferation of smooth muscle cells, antithrombotic and anti-atherosclerotic action in the vessels [13][14][15], reduction of renin secretion, inhibition of sodium reabsorption in the kidneys and weakening of the sclerosis of the glomeruli, renin and pericanalicular interstitium [16,17]. Increased N0 production by endothelial cells, vasodilation, and the antiproliferative effect of all three NUPs also involve C-type receptors that are not associated with GC, but mediate their effects through Gi proteins that inhibit adenylate cyclase activity in target cells, followed by activation of phospholipase C [18,19].…”